D-1,2,3,4-四氢异喹啉-3-羧酸盐酸盐 | 41220-48-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: D-1,2,3,4-四氢异喹啉-3-羧酸盐酸盐
• 英文名称: (3R)-1,2,3,4-terahydroisoquinoline-3-carboxylic acid hydrochloride
• 英文别名: (3R)-1,2,3,4-tetrahydroisoquinole-3-carboxylic acid hydrochloride；(3R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride；(R)-3-carboxy-1,2,3,4-tetrahydroisoquinolin-2-ium chloride；(R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride；D-tetrahydroisoquinoline-3-carboxylic acid hydrochloride；(3R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid;hydrochloride
• CAS: 41220-48-8
• 化学式: C₁₀H₁₁NO₂*ClH
• mdl: MFCD00800581
• 分子量: 213.664
• InChiKey: FXHCFPUEIDRTMR-SBSPUUFOSA-N

物化性质

• 熔点：
  300 °C
• 稳定性/保质期：
  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  -1.21
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.3
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 安全说明：
  S24/25
• 海关编码：
  2933499090
• 储存条件：
  存放于阴凉干燥处。

SDS

Name:	D-1,2,3,4-Tetrahydroisoquinoline-3-Carboxylic Acid Hydrochloride Material Safety Data Sheet
Synonym:	None.
CAS:	41220-48-8

Section 1 - Chemical Product MSDS Name: D-1,2,3,4-Tetrahydroisoquinoline-3-Carboxylic Acid Hydrochloride Material Safety Data Sheet
Synonym: None.

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SECTION 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
41220-48-8	D-1,2,3,4-Tetrahydroisoquinoline-3-Car	ca 100	unlisted

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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SECTION 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW The toxicological properties of this material have not been fully investigated. Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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SECTION 4 - FIRST AID MEASURES
Eyes:
Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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SECTION 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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SECTION 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions. Provide ventilation.

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SECTION 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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SECTION 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low. Exposure Limits CAS# 41220-48-8: Personal Protective Equipment
Eyes:
Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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SECTION 9 - PHYSICAL AND CHEMICAL PROPERTIES
Physical State: Solid
Color: white to off-white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: > 300 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C10H11NO2.HCl
Molecular Weight: 213.66

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SECTION 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Hydrogen chloride, nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported

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SECTION 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 41220-48-8 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
D-1,2,3,4-Tetrahydroisoquinoline-3-Carboxylic Acid Hydrochloride - Not listed by ACGIH, IARC, or NTP.

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SECTION 12 - ECOLOGICAL INFORMATION

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SECTION 13 - DISPOSAL CONSIDERATIONS Dispose of in a manner consistent with federal, state, and local regulations.

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SECTION 14 - TRANSPORT INFORMATION IATA Not regulated as a hazardous material. IMO Not regulated as a hazardous material. RID/ADR
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing group:

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SECTION 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases: S 24/25 Avoid contact with skin and eyes. S 28A After contact with skin, wash immediately with plenty of water. S 37 Wear suitable gloves. S 45 In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible). WGK (Water Danger/Protection) CAS# 41220-48-8: No information available. Canada None of the chemicals in this product are listed on the DSL/NDSL list. CAS# 41220-48-8 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 41220-48-8 is not listed on the TSCA inventory. It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
MSDS Creation Date: 5/03/1999 Revision #2 Date: 5/20/2002 The information above is believed to be accurate and represents the best information currently available to us. However, we make no warranty of merchantability or any other warranty, express or implied, with respect to such information, and we assume no liability resulting from its use. Users should make their own investigations to determine the suitability of the information for their particular purposes. In no way shall the company be liable for any claims, losses, or damages of any third party or for lost profits or any special, indirect, incidental, consequential or exemplary damages, howsoever arising, even if the company has been advised of the possibility of such damages.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  D-1,2,3,4-四氢异喹啉-3-羧酸盐酸盐 在 吡啶 、 盐酸 、 sodium carbonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 ((R)-3-Benzyloxycarbamoyl-3,4-dihydro-1H-isoquinolin-2-yl)-(4-methoxy-phenyl)-phosphinic acid butyl ester
  参考文献：
  名称：

  New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids

  摘要：

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.

  DOI：

  10.1021/jm0103211
• 作为产物：
  描述：

  聚合甲醛 、 D-苯丙氨酸 在 盐酸 作用下， 以 水 为溶剂， 反应 4.0h， 生成 D-1,2,3,4-四氢异喹啉-3-羧酸盐酸盐
  参考文献：
  名称：

  Facile Preparation of optically Pure (3S)- and (3R)- 1, 2, 3, 4-Tetrahydroisoquinoline-3-carboxylic Acid

  摘要：

  光学纯的(3S)-1, 2, 3, 4-四氢异喹啉-3-羧酸(1)通过对其苄基酯(2b)的分馏结晶法轻松获得，该苄基酯是由部分消旋的1盐酸盐制备而成，随后经过催化去苄基化。同样，(3R)-1也是通过相同的程序制备的。在使用光学活性的苯丙氨酸进行Pictet-Spengler反应时，通过在存在手性位移试剂的情况下，对反应产物(1)所得到的相应甲基酯(2a)进行1H核磁共振(1H-NMR)光谱分析，确定了消旋化的程度。

  DOI：

  10.1248/cpb.31.312

文献信息

• Dynamic combinatorial chemistry with hydrazones: libraries incorporating heterocyclic and steroidal motifs
  作者：Mark G. Simpson、Michael Pittelkow、Stephen P. Watson、Jeremy K. M. Sanders

  DOI：10.1039/b917146k

  日期：——

  We expand the possibilities in hydrazone based dynamic combinatorial chemistry with a series of new building blocks incorporating heterocyclic motifs. The synthetic procedure allows efficient access to building blocks with the general structure (MeO)2CH-Heterocycle-C(O)NHNH2, originating from heterocycles with an amine and an ester functionality. The equilibrium distribution of macrocyclic N-acyl hydrazones formed upon deprotection of the building blocks with TFA in organic solvents is reported. The mixing behaviour of these heterocycle-based building blocks with our cholate-based building blocks is described, particularly the observation of kinetic intermediates that disappear following ‘proof-reading’.

  我们通过一系列引入杂环基序的新型构建单元，拓展了基于脒的动态组合化学的可能性。合成程序可以高效地获得具有通用结构 (MeO)2CH-杂环-C(O)NHNH2 的构建单元，这些构建单元源自含有胺和酯官能团的杂环化合物。我们还报道了在有机溶剂中用三氟乙酸对这些构建单元进行去保护后形成的宏环 N-酰基脒的平衡分布情况。此外，描述了这些基于杂环的构建单元与我们基于胆酸盐的构建单元的混合行为，特别是观察到在“校对”后消失的动力学中间体。
• Peptidylaminodiols
  申请人：ABBOTT LABORATORIES

  公开号：EP0189203A2

  公开（公告）日：1986-07-30

  The invention relates to renin inhibiting compounds of the formula: wherein R10 is A is hydrogen or an N-protecting group; w is 0 or 1; B is hydrogen, hydroxy, NH, N-alkyl, loweralkyl or arylalkyl; with the proviso that when w is 1, B is NH and when w is 0, B is hydrogen, hydroxy, loweralkyl or arylalkyl; R1is loweralkyl or lipophilic or aromatic or hydrophilic amino acid side chains; m is 1-3; n is 1-3; p is 1-3; q is 1-3; s is 1-3; t is 0-2; R2 is hydrogen or loweralkyl; R3 and R4 are independently selected from loweralkyl, lipophilic or aromatic amino acid side chains; R5 and R7 are independently selected from hydrogen or loweralkyl; and R6 is hydrogen, loweralkyl, vinyl, arylalkyl or wherein R8 is hydrogen or loweralkyl, X is O, NH or S and R9 is hydrogen, loweralkyl or alkanoyl or XR9 together can be loweralkylsulfonyl, N3 or Cl.

  本发明涉及式中的肾素抑制化合物： 其中 R10 是 A是氢或N-保护基；w是0或1；B是氢、羟基、NH、N-烷基、低级烷基或芳基烷基；但当w是1时，B是NH，当w是0时，B是氢、羟基、低级烷基或芳基烷基；R1是低级烷基或亲油性或芳香性或亲水性氨基酸侧链；m是1-3；n是1-3；p是1-3；q是1-3；s是1-3；t是0-2；R2是氢或低级烷基；R3 和 R4 独立选自低烷基、亲油或芳香族氨基酸侧链；R5 和 R7 独立选自氢或低烷基；R6 是氢、低烷基、乙烯基、芳烷基或其中 R8 是氢或低烷基，X 是 O、NH 或 S，R9 是氢、低烷基或烷酰基或 XR9 合在一起可以是低烷基磺酰基、N3 或 Cl。
• WO2006/55951
  申请人：——

  公开号：——

  公开（公告）日：——
• New Strategy for Antedrug Application:  Development of Metalloproteinase Inhibitors as Antipsoriatic Drugs
  作者：Masaaki Sawa、Takako Tsukamoto、Takao Kiyoi、Kiriko Kurokawa、Fumio Nakajima、Yuichiro Nakada、Koichi Yokota、Yoshimasa Inoue、Hirosato Kondo、Kohichiro Yoshino

  DOI：10.1021/jm010349c

  日期：2002.2.1

  Phosphonamide-based inhibitors were synthesized and evaluated for the inhibitory activities against the shedding of epidermal growth factors, amphiregulin and lieparin-binding EGF-like growth factor, that would participate in the development of psoriasis. All compounds exhibited excellent inhibitory activities for these EGF sheddings; however, they also inhibited matrix metalloproteinases (MMPs). To avoid adverse effects reported by the clinical development of MMP inhibitors, the antedrug concept was introduced. Among the phosphonamide inhibitors, the 2,2,2-trifluoroethyl ester 8d and 2,2-difluoroethyl ester 8c showed rapid decomposition in human plasma, which is an essential property for the antedrug. Topical applications of these compounds significantly suppressed TPA-induced epidermal hyperplasia in murin skin, a model of psoriasis. These results suggested that the phosphonamide-based inhibitors have a therapeutic potential for the treatment of psoriasis as an antedrug application.
• Discovery of Tetrahydroisoquinoline-Containing CXCR4 Antagonists with Improved in Vitro ADMET Properties
  作者：Eric J. Miller、Edgars Jecs、Valarie M. Truax、Brooke M. Katzman、Yesim A. Tahirovic、Robert J. Wilson、Katie M. Kuo、Michelle B. Kim、Huy H. Nguyen、Manohar T. Saindane、Huanyu Zhao、Tao Wang、Chi S. Sum、Mary E. Cvijic、Gretchen M. Schroeder、Lawrence J. Wilson、Dennis C. Liotta

  DOI：10.1021/acs.jmedchem.7b01420

  日期：2018.2.8

  CXCR4 is a seven-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by >= 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4(+) tumor cells from immune surveillance and chemotherapeutic elimination by (1) stimulating prosurvival signaling and (2) recruiting CXCR4(+) immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4 metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated prosurvival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR44(+) cancer cell metastasis. Current small molecule CXCR4 antagonists suffer from poor oral bioavailability and off target liabilities. Herein, we report a series of novel tetrahydroisoquinoline-containing CXCR4 antagonists designed to improve intestinal absorption and off-target profiles. Structure activity relationships regarding CXCR4 potency, intestinal permeability, metabolic stability, and cytochrome P450 inhibition are presented.